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Dostarlimab

 

Dostarlimab is approved for the treatment of patients with recurrent or advanced endometrial cancer that has progressed on or following prior treatment with a platinum-containing chemotherapy and whose cancers are mismatch repair deficient.

 

Tradename Jemperli.

 

It is a  PD-1 checkpoint inhibitor evaluated in a single-arm, multi-cohort trial, data of which showed that, of 71 patients with dMMR recurrent or advanced endometrial cancer, dostarlimab elicited a 42.3% objective response rate (ORR) (GARNET trial).

 

The duration of response (DOR) was at least 6 months for 93% of responders.

 

Objective response rate was 45.5% in patients with dMMR endometrial cancer at a median follow-up of 16.5 months.

 

Recurrent or advanced deficient mismatch repair (dMMR) endometrial cancer was determined by an FDA-approved test.

 

Patients received 500 mg of dostarlimab once every 3 weeks for 4 doses, followed by 1000 mg once every 6 weeks until disease progression.

 

Only 2% of patients discontinued the drug because of treatment-related adverse events.

 

The most common adverse events  were asthenia (15%), diarrhea (15%), fatigue (14%), and nausea (13%).

 

The FDA has granted an accelerated approval to dostarlimab-gxly for the treatment of adult patients with mismatch repair-deficient recurrent or advanced solid tumors, as determined by an FDA-approved test, who have progressed on or following previous treatment and who have no satisfactory alternative options.

 

Accelerated approval to dostarlimab-gxly for the treatment of adult patients with mismatch repair-deficient recurrent (dMMR) recurrent or advanced solid tumors, as determined by an FDA-approved test, who have progressed on or following previous treatment and who have no satisfactory alternative options.

 

Dostarlimab-gxly elicited an objective response rate (ORR) of 41.6% in all dMMR solid tumors, including endometrial and non-endometrial solid tumors, including  a partial response (PR) rate of 32.5%. 

 

The median duration of response (DOR) was 34.7 months, with 95.4% of patients experiencing a response that persisted for 6 months or longer. 

 

In the dMMR solid tumor non-endometrial cancer cohort, the ORR with dostarlimab was 38.7%.

 

Study participants were given dostarlimab via intravenous infusion at a dose of 500 mg once every 3 weeks for 4 total doses; this was followed by a dose of 1000 mg once every 6 weeks. 

 

Treatment was given until either progressive disease or intolerable toxicity.

 

The most frequently experienced adverse effects (AEs), which occurred in 20% or more of patients, included fatigue/asthenia (42%), anemia (30%), diarrhea (25%) and nausea (22%).

 

The most commonly experienced grade 3 or 4 AEs, which were reported in 2% or more of patients, were anemia, fatigue/asthenia, increased transaminases, sepsis, and acute kidney injury. 

 

Grade 3 or 4 laboratory abnormalities, in 2% or more of patients, comprised decreased lymphocytes, decreased sodium, increased alkaline phosphatase. and decreased albumin.

Dostarlimabplus carboplatin-paclitaxel significantly increases progression free survival among patients with primary advanced or recurrent endometrial, cancer, with a substantial benefit in the dMMR-MSI population.

 
 

 

 

 

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